For several years there has been lively controversy over the respective merits of virtual colonoscopy (by computerised X-ray tomography) versus actual colonoscopy in various clinical settings. The basic presumption seems to be that we would rather be exposed to large doses of ionising radiation than be sodomised by a sort of plastic eel. Having submitted to the eel, I would agree with a correspondent to the NEJM that the actual sodomy is less awful than the bowel prep and starvation; in fact it’s rather intriguing to watch the inside of one’s bowel while under the influence of midazolam. However, let’s move on (as the colonoscopist said after taking the biopsy): this big Italian study compared the two kinds of bowel imaging in three high risk groups: those with a family history of bowel cancer, those with previous adenomas, and those with positive faecal occult blood. A thousand brave Italians (with a few satellite Belgians) underwent both procedures within the space of three hours. The negative predictive value for CT colonography was 96% overall, but only 85% for the positive FOB group, who are the ones most likely to be screened in the UK programme. It’s the eel for them, I fear.

http://jama.ama-assn.org/cgi/content/abstract/301/23/2453

Every few months I pay a visit to the academic department of general practice in Oxford, where through the kindness of the Head I rejoice in the honorific title of senior research fellow. Each time I’m on site I get lost in a maze of tall bright new buildings which house genomic people unconnected with my humble avocation. A better location for these gene gnomes would be underground, in some vast clanking Niebelheim like the one overseen by Alberich in Wagner’s Das Rheingold. Down there the Regius Professor could whip them by the flickering light of a thousand VDUs as they ceaselessly search their databases and their multiple arrays and their SNP detectors. But to what end? To perform one gene association study is the labour of years: there have been 26 seeking to establish a link between the serotonin transporter gene (5-HTTLPR), stressful life events, and the risk of depression; fourteen were selected for this meta-analysis: and what they show is that there is no association. Come up into the light, ye doleful gnomes: breathe the free air and learn again to make poorly people better.

http://jama.ama-assn.org/cgi/content/abstract/301/23/2462

The ancient Dutch university of Leiden is famous these days for its studies of the genetics of thrombosis risk - we have all heard of Factor V Leiden, and locally we measure it once as part of a "thrombophilia screen" when people discontinue warfarin after their first venous thromboembolism. Others have measured it in family members of those with this common mutation: and yet others have taken an interest in a much rarer thrombophilic mutation, prothrombin G20210A. In fact the authors of this systematic review from Baltimore found 7777 papers on these topics. They selected 46 and tried to find out what this thousand-fold septiform activity might mean for patient care. Again, the answer is nothing. "There is no direct evidence that testing for these mutations, and the resultant management, reduces VTE related outcomes in individuals who have had VTE or in the probands’ family members who have been tested". O come into the light, ye doleful gnomes of Leiden.

http://jama.ama-assn.org/cgi/content/abstract/301/23/2472

NEJM 18 Jun 2009 Vol 360

Is everyone dead yet? Not you and I, dear Reader, not yet: but for that we cannot thank those responsible for influenza virus containment measures. These would have failed anyway, no doubt, but by golly they made sure of it in the UK, as any of you who have gone through the farce of enacting the HPA protocol will know. For our continued survival we must thank the novel swine-origin influenza A (H1N1) virus itself, the subject of several useful studies and other pieces in this week’s NEJM – something for which the journal can and does congratulate itself with good reason, while The Lancet just moans and waffles. Here is as clear and authoritative account as you are ever going get of the origin of this pandemic, within weeks of its confirmation. For a good summary of flu pandemics generally, see p.2595.

http://content.nejm.org/cgi/content/full/360/25/2605

http://content.nejm.org/cgi/content/full/360/25/2595

The SARS scare and this latest virus have made us all mug up on our virology in the last couple of years, but it’s still a swine to understand why some strains infect the whole world within weeks while others just pick off a few pig farmers in America. As a fascinating editorial on p.2667 points out, H1 viruses are triple assortants of viruses from pigs, humans and birds. They are normally highly infectious from pig to pig but only occasionally spread to humans in close contact with pigs. The paper I refer to here contains case reports, including fatalities, from such sporadic infections with other H1 triple assortant viruses. By contrast, the latest kind, which is best called S-OIV, came from a pig and spreads rapidly from human to human but hardly at all from pig to pig. And all these H1s are probably the result of a catastrophic melding of bird and pig and human flu early in the last century. "The current situation is not ‘1918 again’, it is ‘1918 continued’, in that we are still being infected with the remnants of the 1918 pandemic." In other words, this pandemic is just a ripple, not a new catastrophe; this virus has already learnt that it is more profitable to make people sneeze at each other than to kill them.

http://content.nejm.org/cgi/content/full/360/25/2616

http://content.nejm.org/cgi/content/full/360/25/2666

Streptococci can behave in rum ways, too: it was only in the 1970s that group B infection in the first week after birth became widely recognised as a leading cause of illness and death. The prevention strategy adopted in the USA was to introduce universal antenatal screening for strep B in the birth canal between 35 and 37 weeks of gestation and prophylactic antibiotic administration for those who are culture positive. This was associated with a 65% decrease in incidence between 1993 and 1998. Here’s a progress report up to 2004. Screening rates have nearly doubled, but most babies with strep B disease are now born to mothers who screened negative, showing that although useful, current screening methods are not completely effective.

http://content.nejm.org/cgi/content/abstract/360/25/2626

Lancet 20 Jun 2009 Vol 373

"Crown him, ye morning stars of light, who fixed this floating ball" might be a good line for a hymn to Bill Gates, would-be global fixer, sponsor of this paper on the financing of global health, and naturally a hero (with Melinda) of the glorious tale. (The hymn in question was actually addressed to the Name of Jesus for the Children of Israel by the mad Bishop of Methodism, Edward Perronet, around 1780). And if global health is not fixed, it won’t be for lack of good intentions and massive philanthropism, as detailed here. The policy challenges are discussed at enormous length later on in the journal (p.2137). No talk here of population control or the role of the pharmaceutical industry, however. And yet, with no world revolution likely for a decade or two, we should celebrate the unprecedented outpouring of human goodness that this effort represents with a glass or two of chilled Gavi di GAVI (Global Alliance for Vaccines and Immunization; or else the best white wine growing area in northern Italy).

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60881-3/abstract

I have spent a day in the last week listening to and talking about the latest diabetes trials; not my natural stamping ground, and one that fills me with consternation at the awful evidence base for our clinical decision-making in this immensely important area. Most of these trials are plain bad, this one included, though it does not set a new RECORD. What really bothers me is how difficult it is to get to the actual data in diabetic trials, beyond the spin that is put on them by the investigators – UKPDS being a notorious example, despite its 80+ manifestations in the literature. RECORD is actually quite well written up, but it still manages not to tell us much about the glycated Hbs actually achieved by any of the drug combinations, or how many people actually took rosiglitazone for how long. It was an open-label trial addressing the reasonable question of how people fare if you give them rosi in combination with metformin or a sulfonylurea as opposed to combining the two with the option of adding insulin if they got beyond 8.5% HbA1c. Judging from disclosures subsequently made by the study’s sponsors, GlaxoSmithKline, the figure was about 60% for people staying with rosi to the end (as paid to do) versus about 50% for the controls staying with their specified drugs: statin use rose markedly during the study, more so in the rosi group. And so: we know that in this unblinded study, analysed by intention to treat, rosiglitazone did not increase cardiovascular mortality. But more people got heart failure and many more women got distal fractures. Argue on, and if that interests you, look at the excellent debate in CardioBrief: but as to treating patients, I’m none the wiser, and I’ll continue to avoid rosiglitazone.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60953-3/abstract

BMJ 20 June 2009 Vol 338

It may be that you are more interested than I am in the control of dengue fever, how many people don’t turn up for breast and cervical screening, how "matched" patients fare under private or NHS midwives, the non-effect of statins on elderly pneumonia rates, or which way round to have child car seats fitted: if so, gorge away at this week’s British Medical Journal. I am interested in prognostic research, so the final Altman piece on p.1887 is a must, but I don’t expect you are, so I’ll content myself to comment only on a short but very useful run-through of acute leukaemia in children. I guess it’s the diagnosis we all most dread to make, and to have to break to unsuspecting parents. This piece is written by the doctors I’d actually send such children to, and they begin by pointing out that 85% of them will be cured. They get full marks for looking at the primary care literature and for pointing out the difficulty of making the diagnosis at first presentation. Now and again even the blood film may be misleadingly normal. The prognosis of acute lymphoblastic leukaemia remains better than for acute myeloid leukaemia but even in the latter, survival has risen since the 1980s from 15% to 66% at five years. Chemotherapy for leukaemic children can be pretty ghastly, but at least it gets results.

http://www.bmj.com/cgi/content/extract/338/jun11_1/b2285

Ann Intern Med 16 Jun 2009 Vol 150

If you ferment rice with the red fungus Monascus purpureus, you get a mixture containing various statins, including lovastatin. Apparently there has been a study purporting to show that this red yeast rice does reduce cardiovascular events. This single-centre trial seeks to discover if it can be tolerated by statin-intolerant patients as a "natural" alternative to other lipid-lowering agents. The authors of the study claim success in a double-blinded trial with 31 patients in each arm. But the authors of the accompanying editorial (p.885), who run a large clinic specifically for statin-related muscle problems, say that this contradicts their experience. I don’t think I’ll rush to recommend red rice to any patients.

http://www.annals.org/cgi/content/abstract/150/12/830

Stents began their life in the dental surgery of Charles Stent, but their use has spread from the mouth to virtually every tube in the body, including the renal arteries. People with atherosclerotic renal arteries get renal impairment and hypertension, so they generally end up on an antihypertensive, aspirin and a statin. How about stenting the artery as well? This led directly to death in two of 64 patients and did not improve outcomes. Don’t do it.

http://www.annals.org/cgi/content/abstract/150/12/840

More and more of us will have to undergo colonoscopy at some stage, and that will cause bowel perforation in about one examination in 1,800 – a fact confirmed in this large study of Medicare recipients. Other adverse effects include GI bleeding and cardiovascular events, and tend to be commoner with increasing age and co-morbidity, as you’d expect.

http://www.annals.org/cgi/content/abstract/150/12/849

Statin-related myalgia is such a common problem that I never tire of reading reviews about it, and this one is the most useful I’ve encountered so far. It even suggests how to manage it without resorting to red yeast rice. It contains nice biochemical diagrams with lovely names like geranylgeranylation and ubiquinone. It explains some of the discordance between the randomised trials and our everyday clinical experience. But I think the point best worth remembering is that simvastatin is metabolised by the CYP3A4 isoenzyme and so interacts with all sorts of things like grapefruit juice, amiodarone, cyclosporine and antifungals, whereas rosuvastatin is metabolised by CYP2C9 and has far fewer interactions likely to cause myalgia. Also it allows you to get away with a lot more, including very low dosing or alternate day dosing regimes. About 40% of your statin myalgia sufferers will tolerate a return to the original statin at lower dose, and most of the rest may tolerate another statin if you keep trying.

http://www.annals.org/cgi/content/abstract/150/12/858

Plant of the Week: Kniphofia ‘Wol’s Red Seedling’

A gentleman called Wol Staines raised this really red hot poker, which flowers abundantly from now until late August. There are cool low pokers like "Timothy" for the more tasteful, restrained parts of your garden, but this mid-sized fellow will blaze with orange scarlet wherever your summer composition needs a bit of pep.